The “Classification Criteria for Anti-Synthetase Syndrome (CLASS) Project” sought to develop new, standardized guidelines to diagnose Anti-Synthetase Syndrome (ASSD), a rare autoimmune condition that primarily affects muscles, joints, and lungs and is linked to specific antibodies. This international effort involved experts in rheumatology, pulmonology, dermatology, and neurology to ensure the criteria were accurate, globally applicable, and clinically practical.
Purpose and Background:
ASSD can be challenging to diagnose due to its diverse symptoms and overlap with other conditions. The study aimed to create robust criteria to improve consistency in diagnosis, enable better disease management, and support future research by providing clear definitions for “Probable” and “Definite” ASSD.
Methods:
The researchers combined data-driven approaches with expert consensus to achieve their goals.
1. Literature Review and Data Collection:
•A detailed review of existing literature identified the key symptoms and clinical features of ASSD.
•A database was created using information from 1952 ASSD cases and 2097 control cases (patients with conditions mimicking ASSD). Data included:
•Patient demographics.
•Clinical symptoms (arthritis, myositis, interstitial lung disease, etc.).
•Laboratory test results (including anti-synthetase antibodies).
•All information was stored and analyzed in a centralized database (RedCap).
2. Two Complementary Approaches to Develop Criteria:
•Data-Driven Approach:
•A preliminary statistical analysis identified the most important clinical features of ASSD.
•A multivariate model was created, tested, and validated using patient data. This approach used statistical methods to ensure the criteria were objective and reliable.
•Expert-Driven Approach (MCDA):
•Multicriteria Decision Analysis (MCDA) was used to incorporate expert opinions on the importance of symptoms and lab findings.
•A Steering Committee of 20 leading experts in autoimmune diseases ranked and scored clinical features to develop additional candidate models.
•This process included internal validation using case studies and patient vignettes.
3. Validation Process:
The proposed criteria were rigorously tested:
•Antibody Testing:
•Patient serum samples were tested centrally for anti-synthetase antibodies using a gold-standard method.
•Independent Validation Cohorts:
•Separate patient groups were used to test the accuracy of the criteria, ensuring that the findings applied across diverse populations.
•Consensus Conference:
•A conference using the Nominal Group Technique allowed experts to select the best model. Final criteria were chosen based on validity, ease of use, and real-world applicability.
Results:
The study produced a final set of classification criteria that define two levels of ASSD diagnosis:
1. Probable ASSD:
•Requires at least one core clinical feature:
•Arthritis (joint inflammation).
•Myositis (muscle inflammation).
•Interstitial lung disease (lung scarring or damage).
•Points are assigned for additional features (e.g., skin rashes, fevers, specific test results, or antibodies).
•No antibody testing is required to meet this classification.
2. Definite ASSD:
•Requires the same core clinical features as “Probable ASSD.”
•Also requires confirmation of anti-synthetase antibodies through lab testing.
Accuracy of the Criteria:
•Definite ASSD:
•Sensitivity: 94.3% (ability to correctly identify cases).
•Specificity: 99.7% (ability to exclude non-cases).
•Probable ASSD:
•Sensitivity: 97.5%.
•Specificity: 87.5%.
These results were consistent across independent validation datasets and the gold-standard antibody-tested dataset.
Conclusion:
The CLASS Project successfully established new diagnostic criteria for Anti-Synthetase Syndrome, combining rigorous data analysis with global expert consensus. These criteria are notable for:
1.Global Consensus: Developed by a diverse, international team of experts.
2.Clinical Utility: Designed for ease of use in real-world settings.
3.Accuracy: High sensitivity and specificity ensures a reliable diagnosis.
These new guidelines will help standardize ASSD diagnosis worldwide, improve disease management, and facilitate research into this complex condition. The project was funded by ACR (American College of Rheumatology) and EULAR (European Alliance of Associations for Rheumatology), with the criteria awaiting their approval.